Graham S L, Hoffman J M, Gautheron P, Michelson S R, Scholz T H, Schwam H, Shepard K L, Smith A M, Smith R L, Sondey J M
Department of Medicinal Chemistry, Merck Sharp and Dohme Research Laboratories, West Point, Pennsylvania 19486.
J Med Chem. 1990 Feb;33(2):749-54. doi: 10.1021/jm00164a045.
Derivatives of benzofuran- and indole-2-sulfonamide were prepared for evaluation as topically active ocular hypotensive agents. These compounds were found to be excellent inhibitors of carbonic anhydrase and to lower intraocular pressure in a rabbit model of ocular hypertension. However, the development of these compounds for clinical use was precluded by the observation that they cause dermal sensitization in guinea pigs. A correlation between electrophilicity, as assessed by in vitro reactivity with reduced glutathione, and dermal sensitization potential was further documented.
制备苯并呋喃-和吲哚-2-磺酰胺的衍生物，以评估其作为局部活性降眼压药物的效果。这些化合物被发现是碳酸酐酶的优秀抑制剂，并且在高眼压兔模型中能降低眼压。然而，由于观察到它们在豚鼠中会引起皮肤致敏，这些化合物无法用于临床开发。通过与还原型谷胱甘肽的体外反应性评估的亲电性与皮肤致敏潜力之间的相关性得到了进一步证实。
